Functional and phylogenetic alterations in gut microbiome are linked to graft-versus-host disease severity

From BugSigDB
Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/30
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Payen M, Nicolis I, Robin M, Michonneau D, Delannoye J, Mayeur C, Kapel N, Berçot B, Butel MJ, Le Goff J, Socié G, Rousseau C
Journal
Blood advances
Year
2020
Acute graft-versus-host disease (aGVHD) is the main complication of hematopoietic stem cell transplantation (HSCT). Changes in gut microbiota composition have been associated with subsequent aGVHD, and reconstitution of healthy microbiota is currently being explored as a therapeutic approach. However, the specific actors in the intestinal ecosystem involved in the pathologic process at the time of aGVHD onset are not yet fully known. We prospectively collected stool samples from patients who underwent allogeneic HSCT. Patients sampled at aGVHD onset were compared with non-GVHD patients. To identify phylogenetic and functional signatures of the disease process, we determined fecal short-chain fatty acid (SFCA) profiles and used high-throughput DNA sequencing and real-time quantitative polymerase chain reaction to assess the microbiota composition. Microbiota alterations were highly specific of gastrointestinal (GI) aGVHD severity. Bacterial biomass and α-diversity were lower in severe aGVHD. We identified several bacterial signatures associated with severe aGVHD at disease onset; a negative correlation was observed with anaerobic bacteria of the Lachnospiraceae, especially the Blautia genus, and Ruminococcaceae families. In parallel, in severe aGVHD patients, we showed a dramatic decrease in the levels of the main SFCAs: acetate (75.8%), propionate (95.8%), and butyrate (94.6%). Mild aGVHD patients were characterized by conserved levels of propionate and Blautia propionate producers. Butyrate was significantly decreased in all GI aGVHD stages, representing a potential diagnostic marker of the disease. Specific microbiota and metabolic alterations were thus associated with aGVHD severity and may be useful for diagnostic and pathophysiologic purposes.

Experiment 1


Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/30

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks

Subjects

Location of subjects
France
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
graft versus host disease disease, graft-versus-host,disease, graft-VS-host,disease, homologous wasting,disease, runt,diseases, graft-versus-host,diseases, graft-VS-host,graft versus host disease,graft VS host disease,graft VS. host disease,graft-versus-host disease,graft-versus-host disease, resistance to,graft-versus-host disease, susceptibility to,graft-versus-host diseases,graft-versus-host-disease,graft-VS-host disease,graft-VS-host diseases,GVH,GVHD,GVHDS,homologous wasting disease,runt disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Severe acute graft-versus-host-disease
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients who are diagnosed with severe gut acute graft- versus-host disease (between standard stage greater or equal to 2 and less than or equal to 4)
Group 0 sample size Number of subjects in the control (unexposed) group
35
Group 1 sample size Number of subjects in the case (exposed) group
35

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
4


Alpha Diversity

Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/30

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Claregrieve1, WikiWorks

Source: Figure 2B

Description: Differential relative abundance between controls and severe acute graft-versus- host disease patients.

Abundance in Group 1: increased abundance in Severe acute graft-versus-host-disease

NCBI Links
Lactococcus
Lautropia
Stenotrophomonas
Xanthomonadaceae
Xanthomonadales
Prevotella sp.

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/30

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Claregrieve1, WikiWorks

Source: Figure 2B

Description: Differential relative abundance between controls and severe acute graft-versus- host disease patients.

Abundance in Group 1: decreased abundance in Severe acute graft-versus-host-disease

NCBI Links
Alphaproteobacteria
Anaerostipes
Blautia
Clostridia
Thomasclavelia
Eubacteriales
Flavonifractor
Gemella
Intestinimonas
Lachnoclostridium
Lachnospiraceae
Oscillibacter
Oscillospiraceae
Rhodospirillales
Ruminiclostridium
Sellimonas

Revision editor(s): Claregrieve1, WikiWorks

Experiment 2


Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/30

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks

Subjects

Location of subjects
France
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
graft versus host disease disease, graft-versus-host,disease, graft-VS-host,disease, homologous wasting,disease, runt,diseases, graft-versus-host,diseases, graft-VS-host,graft versus host disease,graft VS host disease,graft VS. host disease,graft-versus-host disease,graft-versus-host disease, resistance to,graft-versus-host disease, susceptibility to,graft-versus-host diseases,graft-versus-host-disease,graft-VS-host disease,graft-VS-host diseases,GVH,GVHD,GVHDS,homologous wasting disease,runt disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Severe acute graft-versus-host-disease
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients who are diagnosed with severe gut acute graft- versus-host disease (between standard stage greater or equal to 2 and less than or equal to 3)
Group 0 sample size Number of subjects in the control (unexposed) group
35
Group 1 sample size Number of subjects in the case (exposed) group
35

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes


Alpha Diversity

Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/30

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Claregrieve1, WikiWorks

Source: Figure 2C

Description: Differential relative abundance between controls and severe acute graft-versus-host disease patients.

Abundance in Group 1: increased abundance in Severe acute graft-versus-host-disease

NCBI Links
Stenotrophomonas
Prevotella

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/30

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Claregrieve1, WikiWorks

Source: Figure 2C

Description: Differential relative abundance between controls and severe acute graft-versus- host disease patients.

Abundance in Group 1: decreased abundance in Severe acute graft-versus-host-disease

NCBI Links
Blautia
Thomasclavelia ramosa
Faecalibacterium sp. UBA1819
Flavonifractor
Lachnoclostridium
Lachnospiraceae
Sellimonas
Oscillospiraceae

Revision editor(s): Claregrieve1, WikiWorks